The effects of myostatin on muscle growth

Whether you’ve heard of myostatin or not, it’s circulating inside your body at this very moment. The tiny myostatin protein conveys a powerful biological message to every muscle cell in your body, and it’s NOT “let’s get ready to grow!” But, that is changing!

THE “SKINNY PROTEIN” IS A CHOKE CHAIN?

As it turns out, myostatin is proving to play a major role in your body’s resistance to bigger muscles, i.e., your failure to grow to the dimensions you truly desire. However, recent technological developments may make it possible for you to enjoy “hypertrophic freedom” soon. (Planet Muscle, of course, will be the first to report on this industry-shaking stuff, as usual.)

As we speak, (or read) myostatin molecules are slotting into receptors on the membrane of your muscle cell. Many thousands of such myostatin-receptor interactions are triggering a flurry of biochemical events that will serve to keep your muscle cells from getting as big and lean as you’d like!

You protest, “But, I work out like a maniac! I eat 300 grams of protein a day!” Yet, your gains in muscle size are unsatisfactory, are they not? Yes, and myostatin has a great deal to do with your frustration.

Choke collar n. A chain collar that tightens like a noose when the leash is pulled. Used to train or control dogs or other animals. Also called choke chain.

Myostatin n. A protein. The product of the myostatin gene that tightens like a noose on the protein-building machinery of muscle cells. Used to limit and restrict muscle growth in adults. Generally detested by bodybuilders. Also called the “skinny protein.”

Myostatin could be regarded as Mother Nature’s “choke collar” on muscle growth [1]. Hence, the name ‘skinny protein’. Myostatin powerfully suppresses the protein-building machinery of your muscle cells, restricting them to a limited degree of growth. In this way, myostatin effectively keeps your muscles from getting bigger than is necessary to cope with the average situation of life (as evolution and natural selection has dictated).

Biological evolution, natural selection, Mother Nature, if you like, favors not the magnificent, but the moderate. The human body got us to this point because it could cope reasonably well with the average situations faced by our ancestors tens to hundreds of thousands of years ago.

This reasonable coping power is programmed into the super-coiled helices of your very own DNA – your chromosomes. Furthermore, these are the same genes that carry much the same messages that they carried in your prehistoric kin. The trouble is, your modern-day wants frequently clash with your biological needs! Bodybuilders desire huge muscles. However, we just don’t have to slay mastodons anymore for meat and skins. So, our desire exceeds what our genes can pony up.

MYOSTATIN = GROWTH MODERATION

Bodybuilding is not about moderation, but rather grandiosity. While myostatin may be helpless at keeping your ego on a leash, it does an exceptional job at restricting the growth of your muscles.

Only with years of exhaustive training (and entire chicken farms of protein) do your hair-like muscle cells show substantial increases in diameter. Even then, the gains can be annoyingly small.

But, do we think that nature could hide a substance that might choke off the choke collar on muscle building? Maybe! The search for a myostatin ‘neutralizer’ is certainly well underway!

MYOSTATIN “KNOCKED OUT”

We know of animals that harbor mutations in the myostatin gene. These animals exhibit dramatically enhanced muscle growth and an equally astonishing reduction in body fat.

Dr. Arnold [2] refers to myostatin “knockout” mice (i.e., mice with a deleted myostatin gene) that display “bulging muscular development visible all over their bodies, with the most extreme hypertrophy apparent in the shoulders and hindquarters….”

These researchers also note that “double-muscled cattle” are even more easily discernable than their murine (mouse) counterparts. “On Belgian Blue Bulls, every intra-muscular groove is readily visible, due to an almost complete lack of subcutaneous fat. Instead of the boxy build of typical cattle, double-muscled animals have tight, greyhound bellies. Indeed, they have a muscular conformation most often reserved for draft horses and bodybuilders.” (Gee, there’s a blatant cry for a retail product!)

Dr. Arnold’s group adds that the dramatic muscle growth seen in myostatin “null” animals is specific to muscle tissue. The hypertrophy is observed throughout the body, and not merely specific to certain regions.

“Is the muscle growth real – does inhibiting myostatin make for muscles that are stronger, too?” This is an important question. Like the muscle tissue in some patients with growth-hormone secreting tumors, will the muscle created by myostatin inhibition be larger than normal, but weaker?

Bogdanovich [3] provides some evidence to suggest that myostatin blockade will result in muscles that are big and proportionally strong! Wow! When these scientists injected mice with muscular dystrophy with an antibody to myostatin, they found that: “[The] increase in muscle strength was proportional to the degree of increase in muscle mass and offers physiological evidence for a functional improvement in [muscular dystrophic] muscle produced by myostatin blockade in vivo.”

CAN MYOSTATIN “NEUTRALIZATION” BE DANGEROUS?

Myostatin belongs to the transforming growth factor (TGF) family of growth factors. Like myostastin, transforming growth factor-beta (TGF-b) can act as a “choke collar” on cell growth. As one industry expert remarked to me “Many substances have an impact on TGF-b pathways, but are hazardous since they can promote growth of malignant cells.”

In other words, if you block myostatin, might you produce runaway cell division, also known as cancer?

The evidence to date suggests that myostatin blockade will not produce cancer. A noted researcher, a Professor of Animal Science and Foods and Nutrition at the University of Georgia, has commented: “Myostatin is also referred to as GDF-8, a subclass of at least 16 growth factors of the TGF gene family. The family of proteins as a composite, has a plethora of actions. There has been no increased incidence of tumors of any kind reported for any of the various types of mice produced where GDF-8 is inhibited, or in any cattle breeds where mutated and/or inactive GDF-8 is produced.” Which means, cancer is doubtful!

INCREASING ANABOLISM, HOW TO INHIBIT MYOSTATIN!

When your body makes, or synthesizes, more muscle protein than it breaks down over time, we generally expect bigger muscles to result.

However, there’s more to it than that. You may have already heard of satellite cells. Think of them as immature muscle cells. Unlike the mature muscle cells that comprise the bulk of your muscle mass, satellite cells can divide to make copies of themselves. This is termed proliferation. These cells can also merge with your mature muscle cells and donate their DNA in times of need.

In fact, the proliferation of your satellite cells is essential for muscle growth [5]. Satellite cell proliferation increases the total amount of DNA in a muscle. With the protein synthesis capacity reflected in the RNA levels, we can measure these two things to get a feel for the anabolic state of a muscle cell, but myostatin certainly figures in this mix.

The centered current belief so far on how to inhibit myostatin goes something like this: Heparin is a carbohydrate (a.k.a. ‘polysaccharide’) that occurs all over your body, especially in the lining of your blood vessels and the spaces between your cells. One of heparin’s building blocks is glucosamine. Heparin often occurs with sulfur attached to it, i.e., heparin sulfate. Thus, heparin sulfate may be referred to as a ‘sulfated polysaccharide’. Many different growth-regulating proteins in your body, including myostatin, can bind to heparin. These heparin interactions may serve to ‘store’ the proteins until they are needed, concentrate them near their receptors (IGF-1 or near the IGF-1 receptor) and/or protect them from inactivation by protein-digesting enzymes.

The sites on the protein, heparin binding sites, are very common in growth-regulating proteins, and have been used to purify myostatin. The myostatin inhibitors currently on the market contain a ‘sulfated polysaccharide’, analogous to heparin sulfate, from a salt water algae. The hopes are that this sulfated polysaccharide binds myostatin better than heparin. Studies are and will be done for clinical proof of efficacy.

Many substances in nature may show myostatin binding activity, and it will take blind and double-blind clinical trials on humans to fully demonstrate the oral activity of such substances, most importantly, an ability to increase muscle mass and reduce fat mass. From theory to practice!

Myostatin seems to circulate in the blood as an inactive, complex [1]. Studies will be explored to see if one consumes enough of a ‘sulfated polysaccharide’ to transient bind a biologically significant amount of myostatin, whether this can have activity if it is already in an inactive complex? No one yet knows for sure, but current and future studies will answer these questions!

WILL THERE BE PROVEN MYOSTATIN NEUTRALIZERS THAT ARE NOT GENETIC MODULATIONS?

“To date, myostatin is the only secreted protein that has been demonstrated to play a negative role in regulating muscle mass in vivo. Although additional experiments will be required to prove aspects of this overall model and to identify the other signaling components, our data suggest that myostatin antagonists, such as follistatin and the myostatin propeptide, or activin type II receptor antagonists may be effective muscle-enhancing agents for both human and agricultural applications.” [6].

Antagonizing myostatin is precisely what some groups (university-based research) are going to, and are, doing right now. Some are developing a number of in vitro (cell-based) assays with which to screen for natural, orally bioavailable products with myostatin-‘neutralizing’ activity. In vivo (whole animal) assays, ultimately involving human beings, will be developed to confirm the findings of the in vitro work. In other words, the future product(s) discovered (in addition to those now) would reach commercial shelves with direct clinical proof of efficacy. And, the claims to augment muscle building and fat removal would have FDA approval.

SUMMARY

Natural Myostatin Neutralizers May Be Capable Of Producing Dramatic…

Increases in muscle mass with a proportional increase in muscle strength.

Reductions in body fat

Increases in caloric output without changing caloric input.

Myostatin neutralization or inhibition in the future, will be substantiated and accompanied with direct clinical proof of efficacy, confirmation of orally bio-available myostatin inhibition by in vitro work and in vivo work, by safety and body composition enhancement (animal models and in human clinical trials).

This data will reflect specific inhibition of myostatin without neutralizing any other cell proliferation/differentiation regulating substances. The potential applications include obesity, type II diabetes, muscular dystrophies and conditions of muscle wasting (e.g., cancer, AIDS, space travel,) bodybuilding and general weight-management.